This project has taken a new direction which includes studies on the origin, mode of action, and metabolism of gamma-hydroxybutyrate, (GHB), a compound which is a normal constituent of mammalian brain and which is of increasing pharmacological interest. When administered in pharmacological doses, GHB produces a flattening of the EEG, a reversible trance-like state and a profound depression of cerebral glucose utilization. This compound is being used clinically in Europe as an anesthetic adjuvant. Preliminary trials indicate that it is effective in the treatment of narcolepsy and may be of use in the treatment of stroke. GHB, and an enzyme capable of metabolizing it, have been found in tissues such as liver and kidney as well as in brain. This enzyme, an NADP ion-linked alcohol oxido-reductanse which interconverts GHB and succinic semialdehyde, has been purified from hamster liver and partially purified from hamster brain. Studies completed on this enzyme include substrate specificity, enzyme kinetics, molecular weight determination, and inhibition studies with the anticonvulsant agents, diphenylhydantoin, amobarbital, and valproate.